Amanda Knox pauses emotionally while speaking during a news conference at Sea-Tac International Airport in Washington after landing there on a flight from Italy, in October 2011. Italy's hightest court ordered a retrial of the American and her Italian former boyfriend for the murder of British student Meredith Kercher, on Tuesday.

Nicosia, Cyprus — Italy’s highest court has ordered that Amanda Knox and her Italian former boyfriend face a retrial for their alleged roles in the murder of Meredith Kercher, potentially extending a highly emotional case that has already lasted six years for many more.

The Supreme Court in Rome overturned the 2011 acquittal of Ms. Knox and her ex-boyfriend, Raffaele Sollecito, for the 2007 murder of the 21-year-old British student in the historic walled town of Perugia.

Knox, who is now 25 and a student at the University of Washington in Seattle, said the decision was “painful” and upsetting. She had “thought the nightmare was over,” said her lawyer, Carlo Dalla Vedova.

Under Italy’s painfully slow, frequently dysfunctional system, it is not unusual for cases to last years, because even after being convicted, defendants are entitled to two levels of appeal.

The retrial will be held in front of an appeals in court in Florence, in the neighboring region of Tuscany, in central Italy. It is likely to start next year.

"It was painful to receive the news," Knox said in a statement, adding that the prosecution case "has been repeatedly revealed to be completely unfounded and unfair."

She did not say whether she would return to Italy for the hearings, but the chances are considered highly unlikely.

Knox has been living in her hometown of Seattle since her acquittal, pursuing her studies and working on a book about her experiences.

The eagerly anticipated memoir, called “Waiting to be Heard,” is due to be published on April 30 and will coincide with her first television interview on the ABC network in the United States.

But she now faces the threat of a request for her extradition from the US back to Italy for the retrial.

Under an extradition treaty agreed in 1984, the two countries are obliged to extradite anyone charged with or convicted of an extraditable offense, or any offense punishable by a prison sentence of more than one year. US law, however, prevents someone from being tried more than once for the same offense.

Rome would have to provide the American authorities with documents to demonstrate they have "probable cause to believe" that Knox was involved in the murder of Kercher.

Her lawyer, Mr. Dalla Vedova, said it was very unlikely she would turn up for the retrial. "If the court orders another trial, if she is convicted at that trial and if the conviction is upheld by the highest court, then Italy could seek her extradition," he told reporters in Rome.

It would then be up to the US authorities to decide whether to accede to the request.

The Supreme Court in Rome could have upheld their acquittals, in which case the saga would have been closed for good.

The judges’ decision to order a retrial is a heavy blow for Knox and Mr. Sollecito, who was meant to be celebrating his 29th birthday on Tuesday.

The Supreme Court, also known as the Court of Cassation, ruled that the grounds for their acquittal were shaky.

The exact reasons for their decision, and the points of law that they have called into question, will not be known until the judges release their full ruling, which will take as many as 90 days.

The pair had served four years behind bars when their murder convictions were overturned by a court in Perugia in 2011.

The appeals court in Perugia criticized many key aspects of the original police investigation and the prosecution’s case.

In particular, they said prosecutors had failed to establish a convincing motive for the killing and that DNA evidence relating to two key bits of evidence – a strap from Kercher’s bra and the alleged murder weapon, a kitchen knife – was inconclusive.

But the presiding judge left many questions about the murder unanswered when he refused to rule on whether the crime was committed by a lone killer or more than one person.

In a 144-page document explaining its ruling, the appeals court said that “it is not this court’s role to suggest how the crime actually unfolded – nor whether there was one perpetrator or more than one.”

Prosecutors alleged that Kercher was killed by Sollecito and Knox as a result of a four-way sex game that spun horribly out of control.

They said the murder was stoked by drugs, domestic friction between Knox and her British housemate, and sexual jealousy.

The other person accused of the crime, Rudy Guede, a local drifter who was born in Ivory Coast but adopted by an Italian family, is serving a 16-year sentence having undergone a separate trial.

Knox, who stayedup until 2 a.m. Seattle time waiting for the court’s decision, said in her statement: “The prosecution responsible for the many discrepancies in their work must be made to answer for them, for Raffaele's sake, my sake, and most especially for the sake of Meredith's family. Our hearts go out to them.

"No matter what happens, my family and I will face this continuing legal battle as we always have, confident in the truth and with our heads held high in the face of wrongful accusations and unreasonable adversity."

Sollecito lives in Verona in northern Italy, where he is studying the use of robotic instruments in surgery. Neither he nor Knox were in court Monday.